RNA interference (RNAi) is a near-ubiquitous pathway involved in post-transcriptional gene modulation. A key effector molecule of RNAi is the microRNA (miRNA or miR). These small, non-coding RNAs are transcribed as primary miRNAs (pri-miRNA) and processed in the nucleus by Drosha (a Type III ribonuclease) to generate short hairpin structures referred to as pre-miRNAs. The resulting molecules are transported to the cytoplasm and processed by a second nuclease (Dicer) before being incorporated into the RNA Induced Silencing Complex (RISC). Interactions between the mature miRNA-RISC complex and messenger RNA (mRNA), particularly between the seed region of the miRNA guide strand (nucleotides 2-7) and regions of the 3′ UTR of the mRNA, leads to gene knockdown by transcript cleavage and/or translation attenuation.
MicroRNAs frequently occur in clusters on chromosomes. MicroRNA clusters fall into two distinct categories: clusters where the individual miRNAs are derived from processing of a common (polycistronic) transcript, and clusters where the individual miRNAs are not derived from a common transcript but are instead co-transcribed because they are regulated by common factors. Using distance-based criteria, 46 miRNA clusters have been identified, containing a total of about 110 miRNAs. The functional relevancy of the clustering of microRNAs has not been adequately established by prior art techniques.